Bortezomib Plus Rituximab for Initial Therapy of EBV+ PTLD

Status: Recruiting
Phase: Phase 2
Diagnosis: Other Trials
NCT ID: NCT01058239 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 09-346

 

Post transplant lymphoproliferative disease (PTLD) is a type of B-cell non-Hodgkin lymphoma that occurs in patients with weakened immune systems due to immunosuppressive medications taken after organ or stem cell transplantation. This is usually related to a virus called Epstein-Barr (EPV). Rituximab is a type of drug called an "antibody" that specifically destroys both normal and cancerous B-cells, and is commonly used for PTLD. Bortezomib is a drug that has been approved by the Food and Drug Administration (FDA) to treat multiple myeloma and a B-cell non-Hodgkin lymphoma called Mantle Cell Lymphoma, and shows significant activity in lymphoma cells caused by EBV. In this research study, we hope to learn if the addition of bortezomib to rituximab treatment can increase the rate of complete remissions and cures of PTLD after organ or stem cell transplant.

 

Conducting Institutions:
Beth-Israel Deaconess Medical Center, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital

Overall PI:
Robin Joyce, MD, Beth Israel Deaconess Medical Center

Site-responsible Investigators:
Jeremy Abramson, MD, Massachusetts General Hospital
Ann LaCasce, MD, Dana-Farber Cancer Institute

Contacts:
Beth-Israel Deaconess Medical Center: Cancer Trials Call Center, 617-667-3060
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

Eligibility Criteria

Inclusion Criteria: - Patients must have had a prior solid organ or allogeneic stem cell transplant. - Patients must have histologically confirmed CD20+ B-cell PTLD diagnosed according to WHO criteria. PTLD may be characterized as early lesions, PTLD/polymorphic, PTLD/monomorphic, or PTLD/other, all of which are eligible for this trial. B-cell PTLD must be associated with EBV as demonstrated either by detection of EBV antigens in tumor samples, or by increased EBV quantitative viral load in serum. - Patients must have measurable disease - Patients should have had an incomplete response after reduction in immunosuppression, or inability to reduce immunosuppression at the discretion of the investigator. Reduction in immunosuppression should be initiated at least 2 weeks but not more than 12 weeks before the time of entry into the study. - Patients who have had reduction in immunosuppression must have evidence of an incomplete response or no response to this strategy by radiographic imaging or bone marrow biopsy. - Patients who are unable to undergo reduction in immunosuppression will also be eligible for inclusion into the trial. Patients are allowed to be on stable doses of glucocorticoids. - 18 years of age or older - Estimated life expectancy of > 3 months - ECOG Performance status of 0, 1, or 2 - Adequate organ and marrow function - Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Exclusion Criteria: - Patients who have had chemotherapy or monoclonal antibody therapy as prior treatment for PTLD. - Patients receiving any other study agents. Patients already on prophylactic doses of ganciclovir or valganciclovir because of a prior history of CMV infection or because of risk factors for CMV infection are eligible for the study and may continue CMV prophylaxis. - Patients with known brain metastases or central nervous system (CNS) involvement of their lymphoma. - Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib, rituximab, ganciclovir or valganciclovir. - Patients with Grade 2 or greater neuropathy within 14 days before enrollment. - Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. - Psychiatric illness/social situations that would limit compliance with study requirements. - Pregnant or breastfeeding women - Individuals with a history of malignancy are ineligible except for those outlined in the protocol - Known HIV positive individuals - Active HBV infection may be included only if they are on appropriate anti-hepatitis B therapy and have an undetectable HBV viral load - Patient has received other investigational drugs within 14 days before enrollment
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